Comprehensive investigation into cuproptosis in the characterization of clinical features, molecular characteristics, and immune situations of clear cell renal cell carcinoma.
Comprehensive investigation into cuproptosis in the characterization of clinical features, molecular characteristics, and immune situations of clear cell renal cell carcinoma.
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关于铜死亡在透明细胞肾细胞癌临床特征、分子特性及免疫状况表征中的综合研究
DOI：
10.3389/fimmu.2022.948042
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发表时间：
2022
影响因子：
7.3
通讯作者：
Shao, Pengfei
中科院分区：
文献类型：
--
作者：
Wang, Bao;Song, Qiang;Wei, Yuang;Wu, Xiangzheng;Han, Tian;Bu, Hengtao;Tang, Sensheng;Qian, Jian;Shao, Pengfei
铜诱导的细胞死亡作为程序性细胞死亡（PCD）的一种形式在人类疾病中得到了广泛的研究。铜诱导的细胞死亡机制的新认识为我们提供了创造性的见解铜相关的细胞毒性，这种形式的PCD被称为铜中毒。通过一致性聚类分析，将TCGA数据库中的ccRCC患者分为具有不同铜中毒分子模式的不同亚组。相应地对亚组进行临床意义、长期生存和免疫特征分析。构建了基于铜中毒的风险特征和列线图，并根据ccRCC队列进行了验证。生成铜中毒评分系统以更好地表征ccRCC患者。最后，使用ccRCC临床样品和细胞系进行体外验证。来自不同亚组的患者表现出不同的临床病理特征、生存结局、肿瘤微环境（TME）特征、免疫相关评分和治疗反应。预测模型和铜中毒评分能有效区分高危/评分和低危/评分患者，具有较高的预测价值。铜中毒评分也倾向于与ccRCC患者的预后和免疫特征密切相关。此外，中枢铜中毒相关基因（CAG）FDX 1在人ccRCC样本中呈现出失调的表达模式，并证实其可有效促进铜离子载体elesclomol作为直接靶点的杀伤作用。体外功能测定揭示了FDX 1在ccRCC中的突出抗癌作用。铜中毒在调控ccRCC的TME特征、肿瘤进展和长期预后中起着不可或缺的作用。
Copper-induced cell death has been widely investigated in human diseases as a form of programmed cell death (PCD). The newly recognized mechanism underlying copper-induced cell death provided us creative insights into the copper-related toxicity in cells, and this form of PCD was termed cuproptosis. Through consensus clustering analysis, ccRCC patients from TCGA database were classified into different subgroups with distinct cuproptosis-based molecular patterns. Analyses of clinical significance, long-term survival, and immune features were performed on subgroups accordingly. The cuproptosis-based risk signature and nomogram were constructed and validated relying on the ccRCC cohort as well. The cuproptosis scoring system was generated to better characterize ccRCC patients. Finally, in vitro validation was conducted using ccRCC clinical samples and cell lines. Patients from different subgroups displayed diverse clinicopathological features, survival outcomes, tumor microenvironment (TME) characteristics, immune-related score, and therapeutic responses. The prognostic model and cuproptosis score were well validated and proved to efficiently distinguish the high risk/score and low risk/score patients, which revealed the great predictive value. The cuproptosis score also tended out to be intimately associated with the prognosis and immune features of ccRCC patients. Additionally, the hub cuproptosis-associated gene (CAG) FDX1 presented a dysregulated expression pattern in human ccRCC samples, and it was confirmed to effectively promote the killing effects of copper ionophore elesclomol as a direct target. In vitro functional assays revealed the prominent anti-cancer role of FDX1 in ccRCC. Cuproptosis played an indispensable role in the regulation of TME features, tumor progression, and long-term prognosis of ccRCC.
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影响因子：
5.9
作者：
Liu YL;Bager CL;Willumsen N;Ramchandani D;Kornhauser N;Ling L;Cobham M;Andreopoulou E;Cigler T;Moore A;LaPolla D;Fitzpatrick V;Ward M;Warren JD;Fischbach C;Mittal V;Vahdat LT
通讯作者：
Vahdat LT
影响因子：
7.3
作者：
Tardito, Saverio;Barilli, Amelia;Marchio, Luciano
通讯作者：
Marchio, Luciano
影响因子：
56.9
作者：
Tsvetkov, Peter;Coy, Shannon;Petrova, Boryana;Dreishpoon, Margaret;Verma, Ana;Abdusamad, Mai;Rossen, Jordan;Joesch-Cohen, Lena;Humeidi, Ranad;Spangler, Ryan D.;Eaton, John K.;Frenkel, Evgeni;Kocak, Mustafa;Corsello, Steven M.;Lutsenko, Svetlana;Kanarek, Naama;Santagata, Sandro;Golub, Todd R.
通讯作者：
Golub, Todd R.
DOI：
10.1038/nrdp.2017.9
发表时间：
2017-03-09
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Hsieh JJ;Purdue MP;Signoretti S;Swanton C;Albiges L;Schmidinger M;Heng DY;Larkin J;Ficarra V
通讯作者：
Ficarra V
DOI：
10.1016/j.omtn.2021.05.009
发表时间：
2021-09-03
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Bai D;Feng H;Yang J;Yin A;Lin X;Qian A;Sugiyama H
通讯作者：
Sugiyama H